Editor’s Note: CardioBrief is pleased to publish this guest post written by James Stein, a professor of medicine at the University of Wisconsin and the director of preventive cardiology at the University of Wisconsin Hospital and Clinics. This post is accompanied by a separate post by Larry Husten.

Universal Screening for Dyslipidemia in Children: A Debate with Equipoise, but Tarnished by Industry Influence

by James H. Stein, MD

As a strong proponent of heart and vascular disease prevention and a parent of two teenagers, I have watched closely the debate about the new Pediatric Lipid Guideline recommendation for universal lipid screening at ages 9-11 years (1-5). The physicians and researchers on both sides of issue are intelligent, thoughtful, and honest advocates for their positions regarding universal screening, a question that truly has scientific equipoise. In this post, I will briefly describe my position, and hopefully sound a clarion about the influence of the medical industry on this debate. My discussion of industry’s role will emphasize evidence from the social science literature about conflicts of interest, so we can move beyond name-calling, moralizing, and emotional responses to this serious issue.

Universal Screening for Dyslipidemia in Children

I oppose universal lipid screening for children, primarily for the reason that Matt Gillman so eloquently described: because “the harms of screening fall disproportionately on the healthy” (2,5). To be clear, the potential harms of universal lipid screening in children, just like its potential benefits, have never been proven. So we are operating in a data vacuum and have scientific equipoise. What are the potential harms? First, increased medical costs, which are born by society, and second, the “medicalization” of lipid values that make children at no short- or even intermediate-term risk of cardiovascular disease (CVD) events, in some way, abnormal. Risks of “medicalization” include stigmatization, labeling, and the practical inconvenience of having every 9-11 year child fast for 12 hours, twice, to get poked with a needle, when the most likely outcome is that they’ll be told that they need to eat a healthy diet and exercise. Of more concern is the astute point raised by Newman et al. that girls have higher cholesterol levels and are more likely to get labeled and treated, but paradoxically are at lower CVD risk (2). In regard to dietary interventions like the CHILD-1 diet, it is not clear to me why healthy eating patterns would not be recommended to all children and families, regardless of their lipid status. In regard to the safety of statins in children, I would argue that the evidence base is slim and likely biased. What is known about their efficacy in children is limited to their effects on surrogate markers. Although it is likely that long term use of statins will reduce CVD risk in children with hyperlipidemia, we have to be honest and recognize that changes in lipid levels and carotid intima-media thickness are not the same as reductions in CVD event rates. The chain of evidence is present, but the links are weak. Accordingly, we have scientific equipoise, not the scientific basis for a strong public health recommendation.

One good point for universal screening – previously raised by Marilyn Mann in a comment on Cardiobrief.org – is that after kids leave home, they often drop out of medical care for a time, so it is easier to identify them when young, even if they do not get treated. It is a fair point, but in my opinion, does not justify screening all children, to find the small number of kids with familial hypercholesterolemia (FH) who would not have been identified by targeted screening. However, this is a question that could be addressed, in part, by mathematical modeling (2). The guideline writers would have strengthened their case if they had presented an analysis of the number of new FH cases identified with universal screening, the number of cases of “dyslipidemia” identified, the number of true and false positives and negatives, as well as the costs and effectiveness of the screening program that they proposed. It would be a challenging and imperfect analysis, but one that should have been done before the guideline was approved, rather than being left to future researchers.

For the record, I have declined to have my kids screened, even though we are in a purportedly higher risk group (Ashkenazi Jews).

The Influence of Industry on the Universal Screening Debate

The debate about universal screening is a fair and important one, but the influence of industry interferes with our ability – indeed, our obligation – to honestly debate and discuss this important public health issue. It is amazing that every time the specter of conflict of interest is raised, doctors and researchers get pretty edgy. You can literally see the hairs rise on their backs. And of course, everyone is an expert on this issue and no one is biased. That is unfortunate, because a strong social science literature has taught us that everyone is biased (6). To illustrate this point, let’s focus on some of the guidelines writers’ responses.

The guideline writers’ contention that “Medical treatment recommendations are based on multiple randomized trials of statin therapy in children with FH demonstrating acceptable safety and efficacy over periods up to 2 years”… rings hollow (3). Almost all of those studies were sponsored and conducted by pharmaceutical companies, including several that have been investigated and even sanctioned for improper handling and reporting of data, including safety data. The studies had small sample sizes and were of short duration, and therefore tell us very little about long-term safety of statins in children and young adults. I am sure that the limitations of these studies would be easy fodder at any medicine or pediatrics resident journal club. But the guideline panel uses these studies as high level evidence to support their deeply held belief in statin safety and their desire to prevent CVD. Preventing CVD is laudable, but one must ask where their belief in long-term statin safety came from when the power of the evidence base to detect even common side effects in children and young adults, is limited and only of about 2 years duration. It likely came from repeated encounters with the pharmaceutical industry, which has inundated us with statin safety messages, as well as our own belief in what we do. These are unconscious, intellectual biases that we, as humans, all succumb too. They are even more insidious when an external influence – in this case the pharmaceutical industry – suggests them to us.

Even more dangerous to the academic mission and our societal obligation to have an open and honest debate is the effect of financial conflict of interest. Here the guideline writers reacted emotionally, rather than responding intellectually. In response to the concern about financial conflicts of interest, the guideline writers state: “To contest the integrity of panel members and their deliberations without evidence is unfair and uninformed.” But actually, it is not. It is their response that is uninformed. The guideline writers’ response is moralistic and defensive, rather than academic. I understand how people get defensive when the issue of financial conflict of interest is raised, but no one is impugning anyone in this debate or challenging their integrity for having a potential conflict of interest. All of these individuals are good, honest physicians and researchers, doing their best to come up with helpful public health guidelines to prevent CVD. In that regard, we all are on the same team. But when people have financial relationships, the data demonstrate that they engage in unintentional motivated reasoning – ie, they become biased (6,7). They can’t help it. It is a by-product of being a human being. Humans are living, breathing, bias machines. We all try to manage our biases, but sometimes we can’t. The key point is that bias is unconscious and does not imply malfeasance or wrong-doing. We just can’t help it. And disclosure, although laudable, does not solve the problem of bias because the problem is not secrecy – it is power (8). Indeed, disclosure may even have the “perverse” effect of increasing bias (7). In this regard, a major problem with the pediatric lipid guidelines is that they did not follow best practices for managing potential conflicts of interest (1,9).

Here’s to an honest, intellectual debate on an important public health topic. Although I oppose universal screening, I am willing to discuss and debate it, ask for more evidence, and recognize its potential advantages and weaknesses. But I suggest we leave the pharmaceutical and device/testing industry out of it, to minimize (not eliminate) the biases and to increase the level of civility in our deliberations.

James H. Stein, MD

Professor of Medicine, Cardiovascular Medicine Division

University of Wisconsin School of Medicine and Public Health

Director, Preventive Cardiology

University of Wisconsin Hospital and Clinics

Disclosures: In the past 3 years I have served on Data and Safety Monitoring Committees for Abbott, Lilly, and Takeda. I receive royalties from the Wisconsin Alumni Research Foundation for a patent regarding ultrasound and CVD risk assessment.

1. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: Summary report. Pediatrics. 2011;128 (suppl 5):S213–S256.

2 comments

Very much appreciate this piece. Although often used as a term of opprobrium, a “conflict of interest” means only that–one is serving interests that may, at the least, distract from each other. On the one hand, to do the best science possible. On the other hand, to reciprocate, identify with, etc. recognition and those who provide it.

The science shows almost universally that COIs affect outomes–not for everyone in every situation, but often enough to make a significant difference. And not, except in unusual instances, because of corruption, but because of human nature–including some of its finer virtues.

As Dr. Stein says eloquently, the unscientific thing is to deny the science. And the policy that follows is to clear the field for what is already complicated enough.